Interleukin-15 Is Critical in the Pathogenesis of Influenza A Virus-Induced Acute Lung Injury
Interleukin-15 Is Critical in the Pathogenesis of Influenza A Virus-Induced Acute Lung Injury
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DOI：
10.1128/jvi.02030-09
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发表时间：
2010-06-01
影响因子：
5.4
通讯作者：
Yoshikai, Yasunobu
中科院分区：
文献类型：
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作者：
Nakamura, Risa;Maeda, Naoyoshi;Yoshikai, Yasunobu
高致病性甲型流感病毒引起急性重症肺炎，“细胞因子风暴”的发生已被提出贡献。在这里，我们发现白细胞介素-15 （IL-15）敲除（KO）小鼠在感染流感病毒A/FM/1/47 （H1N1，一种小鼠适应株）后死亡率降低，尽管这些小鼠的病毒滴度与对照组小鼠没有差异。感染IL-15 KO小鼠肺中抗原特异性CD44(+) CD8(+) T细胞明显减少，CD8(+) T细胞过继性转移导致IL-15 KO小鼠在流感病毒感染后存活降低。基因靶向导致β(2)-微球蛋白缺失的小鼠和体内注射抗CD8单克隆抗体导致CD8(+) T细胞缺失的小鼠感染后死亡率降低。这些结果表明，il -15依赖性CD8(+) T细胞至少在甲型流感病毒引起的急性肺炎发病机制中起部分作用。
Highly pathogenic influenza A viruses cause acute severe pneumonia to which the occurrence of "cytokine storm" has been proposed to contribute. Here we show that interleukin-15 (IL-15) knockout (KO) mice exhibited reduced mortality after infection with influenza virus A/FM/1/47 (H1N1, a mouse-adapted strain) albeit the viral titers of these mice showed no difference from those of control mice. There were significantly fewer antigen-specific CD44(+) CD8(+) T cells in the lungs of infected IL-15 KO mice, and adoptive transfer of the CD8(+) T cells caused reduced survival of IL-15 KO mice following influenza virus infection. Mice deficient in beta(2)-microglobulin by gene targeting and those depleted of CD8(+) T cells by in vivo administration of anti-CD8 monoclonal antibody displayed a reduced mortality rate after infection. These results indicate that IL-15-dependent CD8(+) T cells are at least partly responsible for the pathogenesis of acute pneumonia caused by influenza A virus.